PDF(Pubmed)
Abstract：
Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/β-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and β-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3β inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.
摘要：
柯萨奇病毒A10（CV-A10）感染，儿童手足口病（HFMD）的主要原因，经常表现为耐人寻味的甲癣现象，以指甲脱落为特征。然而,潜在的机制是难以捉摸的。这里,我们发现小鼠的CV-A10感染可以通过抑制LDL受体相关蛋白6(LRP6)磷酸化和β-catenin积累来抑制Wnt/β-catenin信号传导,并导致甲癣。机械上,CV-A10模拟Dickkopf相关蛋白1（DKK1）与含Kringle的跨膜蛋白1（KRM1）相互作用，CV-A10细胞受体。我们进一步发现Wnt激动剂(GSK3β抑制剂)CHIR99021可以恢复指甲干细胞分化并防止指甲脱落。这些发现为CV-A10和相关病毒在甲癣中的发病机制提供了新的见解，并指导该疾病的预后评估和临床治疗。
